【摘 要】
：
Checkpoint kinase 1(Chk1) is a Ser/Thr kinase that is involved in mediating the cellular response to DNA-damage.Inhibition of Chkl has been shown to abrogate DNA damage induced cell cycle arrest,allow
【机 构】
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ZJU-ENS Joint Laboratory of Medicinal Chemistry,College of Pharmaceutical Sciences,Zhejiang Universi
【出 处】
：
第九届IUPAC化学生物学国际研讨会暨第八届世界华人药物化学研讨会
论文部分内容阅读
Checkpoint kinase 1(Chk1) is a Ser/Thr kinase that is involved in mediating the cellular response to DNA-damage.Inhibition of Chkl has been shown to abrogate DNA damage induced cell cycle arrest,allowing cells to advance through the cell cycle without repairing DNA damage leading to mitotic catastrophe and cell death or apoptosis.Therefore it provides an attractive therapeutic target for anticancer combination therapy.PF-00477736 is a potent Chk1 inhibitor in clinical trials.The structural features of the Chk1 small molecule inhibitors are comprised of a planar heterocyclic ring to facilitate the favorable hydrophobic contacts,an amide/urea side chain to interact with the hinge region,and a hydrophilic side chain extending towards the ribose binding pocket.
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